Objective To examine the hypoglycemic effect of Chinese yam polysaccharide on the 3T3-L1 insulin resistance cell model. Methods IR-3T3-L1 adipocytes were randomly divided into control group ( Con), model group (DEX), metformin group (Met, positive drug group) and CYPS group (0. 05, 0. 15, 0. 45 mg / mL). After the creation of the IR-3T3-L1 cell model by dexamethasone (DEX) (1 μmol / L) stimulation, Chinese yam polysaccharide treatment was applied. Glucose intake and the levels of TC, TG, LDL-C, HDL-C, GSH-Px, MDA, HK, and PK were then measured.AMPK-PI3K/ Akt signaling pathway-associated gene expression was identified using qRT-PCR. Results The glucose consumption of IR-3T3-L1 cells was considerably decreased after 48 hours of treatment with 1 μmol / L DEX compared to that of the Con group (P<0. 01), and the reduction persisted for 60 hours. 0. 05, 0. 15, 0. 45 mg / mL CYPS treatment significantly increased glucose consumption (P<0. 01), HK, PK, GSH-Px enzyme activities (P<0. 01), HDL-C content (P<0. 01), and decreased MDA enzyme activity (P<0. 01), T-CHO, TG, LDL-C content (P<0. 01) in IR-3T3-L1 cells. 01). Additionally, CYPS administration dramatically decreased PI3K, Akt, GLUT-4, AMPK, IRS-2, PPARa, and adiponectin mRNA expression levels (P<0. 05) and reduced IRS-1, GSK-3β, ACC, and FAS mRNA expression levels (P<0. 01). Conclusions In IR-3T3-L1 cells, CYPS can reduce oxidative stress, control lipid metabolism disorders, and enhance DEX-induced glucose intake. AMPK-PI3K/ Akt signaling pathway-associated genes may be connected to the process.